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OP14 Improved endoscopic outcomes and mucosal healing of upadacitinib as an induction therapy in adults with moderately to severely active ulcerative colitis: data from the U-ACHIEVE study

W. J. Sandborn*1,1, S. Schreiber2, S. D. Lee3, J. O. Lindsay4, X. Hebuterne5, W. Zhou6, F. Cataldi6, A. P. Lacerda6, B. Huang6, W. Xie6, E. V. Loftus Jr7

1University of California San Diego, La Jolla, USA, 2University Hospital Schleswig-Holstein, Kiel, Germany, 3University of Washington, Seattle, USA, 4Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK, 5Service de Gastroentérologie et Nutrition Clinique, Nice, France; Université de Nice-Sophia-Antipolis, Nice, France, 6AbbVie Inc., North Chicago, USA, 7Mayo Clinic, Rochester, USA

Background

The efficacy and safety of upadacitinib, an oral, selective Janus Kinase 1 inhibitor, was assessed in an 8-week Phase 2 induction study of patients with moderately to severely active ulcerative colitis who had inadequate response, loss of response or intolerance to corticosteroids, immunosuppressants, or biologic therapies.1 This analysis evaluated the endoscopic improvement, endoscopic remission, histological improvement, histological remission, and mucosal healing rates at Week 8 of the U-ACHIEVE study.

Methods

Adult patients with Adapted Mayo Score (Mayo score without Physician Global Assessment) of 5–9 points and centrally read endoscopy subscore of 2–3 were randomised to receive extended-release upadacitinib 7.5, 15, 30, 45 mg once daily (QD) or placebo for 8 weeks. Patient randomisation was stratified by previous biologic use, baseline corticosteroid use, and baseline Adapted Mayo score (≤7/>7). The proportion of patients who achieved endoscopic improvement (endoscopic subscore ≤1), endoscopic remission (endoscopic subscore of 0), histological improvement (any decrease from baseline in Geboes score), histological remission (Geboes score <2), and mucosal healing (endoscopic subscore of 0 AND Geboes score <2) were analysed and pairwise comparisons between upadacitinib doses and placebo were conducted using the Cochran–Mantel–Haenszel test stratified by randomisation factors. Non-responder imputation was utilised for missing values.

Results

A total of 250 patients were randomised with a mean (SD) age of 42.3 (14.2) years and a mean (SD) disease duration of 8.2 (2.5) years. At baseline, 77.6% had prior use of biologics, 36% had an Adapted Mayo Score >7, and 79% had an endoscopic subscore of 3. At Week 8, a dose–response relationship was observed for all efficacy endpoints. The proportion of patients achieving endoscopic improvement, endoscopic remission, histological improvement, histological remission, and mucosal healing was statistically significantly higher (p < 0.05) in the upadacitinib 30 and 45 mg QD groups vs. the placebo group (Table).

Abstract OP014 – Table. Proportion of patients achieving endoscopic improvement, endoscopic remission, histological improvement, histological remission, and mucosal healing at Week 8.

Conclusion

In this dose-ranging 8-week induction study, upadacitinib 30 and 45 mg QD consistently demonstrated significant improvement in endoscopic outcomes, histological outcomes, and mucosal healing compared with placebo in patients with moderately-to-severely active ulcerative colitis.

Reference

1. Sandborn WJ. Efficacy and safety of upadacitinib as an induction therapy for patients with moderately-to-severely active ulcerative colitis: data from the phase 2b study U-ACHIEVE, United European Gastroenterology (UEG) Week, Presentation #OP195, 2018.